Exposure to Per- and Polyfluoroalkyl Substances and Abnormal Glycometabolism in Healthy Elderly: Multiomics Evidence from the China BAPE Study

Mounting evidence suggests that per- and polyfluoroalkyl substances (PFASs), are key drivers of glycometabolism disorders. However, the extent to which this association persists in the elderly population, as well as the underlying mechanisms involved, remains insufficiently characterized. This study aimed to comprehensively investigate associations between PFASs exposure and glycometabolic markers in the healthy elderly using integrated multiomics approach, elucidating underlying biological mechanisms. A panel study was conducted among 76 healthy elderly aged 60-69 years living in Jinan City, China, with five consecutive monthly surveys. Blood concentrations of nine PFASs and five glycometabolic markers were measured. Associations between both individual and combined exposures to PFASs and glycometabolic markers were investigated through a linear mixed-effects model (LMM) and Bayesian kernel machine regression (BKMR). Integrated multiomics analysis delineated mechanisms by which PFASs exposure disrupts glycometabolism. We observed that a single exposure to perfluorobutanoic acid (PFBA) was significantly associated with increases in all five glycometabolic markers. Exposure to perfluorodecanoic acid (PFDA) and perfluorohexanesulfonic acid (PFHxS) was associated with increases in fasting plasma glucose (FPG) and glycated serum protein (GSP), while PFHxS was additionally associated with the triglyceride-glucose index (TyG). Furthermore, the BKMR model further indicated a synergistic and positive association between PFAS mixtures and these markers. Multiomics analyses identified 48 canonical pathways potentially mediating these metabolic disruptions. These findings highlight the need to prioritize reduction of PFASs exposure as a public health strategy for preventing and managing type 2 diabetes mellitus (T2D), particularly in aging populations worldwide.